Methods for targeted drug delivery
View Patent ↗A method for ligand-based binding of lipid encapsulated particles to molecular epitopes on a surface in vivo or in vitro comprises sequentially administering (a) a site specific ligand activated with a biotin activating agent; (b) an avidin activating agent; and (c) lipid encapsulated particles activated with a biotin activating agent, whereby the ligand is conjugated to the particles through an avidin-biotin interaction and the resulting conjugate is bound to the molecular epitopes on such surface. The conjugate is effective for imaging by x-ray, ultrasound, magnetic resonance or positron emission tomography. Compositions for use in ultrasonic imaging of natural or synthetic surfaces and for enhancing the acoustic reflectivity thereof are also disclosed.
1. A method to effect delivery of a therapeutic agent into a target tissue of a subject in vivo which method comprises
(a) administering to said subject an emulsion of particles that consist of lipid-coated liquid perfluorocarbon and at least one therapeutic agent which particles are directly coupled to a ligand specific for said target tissue, and
(b) delivering said therapeutic agent to said target tissue while said particles are entirely in the liquid state.
2. The method of claim 1 wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.
3. The method of claim 2 wherein the ligand comprises an antibody or fragment thereof or a receptor agonist or antagonist.
4. The method of claim 3 wherein the ligand is an antibody or fragment thereof.
5. The method of claim 1 wherein the therapeutic agent is a drug or a radioactive agent.
6. The method of claim 5 wherein the drug is tissue plasminogen activator, adriamycin, vincristine, urokinase, streptokinase, methotrexate, cytarabine, thioguanine, 5-fluorouracil, cisplatin, etoposide, ifosfamide, asparaginase, deoxycoformycin or hexamethyl melamine.
7. The method of claim 1 which further comprises obtaining an ultrasonic image or magnetic resonance image of said target tissue.
8. The method of claim 1 wherein said target tissue is a thrombus or cancer.
9. An emulsion which comprises particles consisting of liquid perfluorocarbon coated with lipid and at least one therapeutic agent, wherein said particles are directly coupled to a ligand specific for a target tissue, wherein said perfluorocarbon consists of perfluorotributylamine, perfluorodecalin, perfluorooctylbromide, perfluorodichlorooctane, perfluorodecane, perfluorotripropylamine, perfluorotrimethylcyclohexane, or mixtures of the foregoing.
10. The emulsion of claim 9 wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.
11. The emulsion of claim 10 wherein the ligand comprises an antibody or fragment thereof or a receptor agonist or antagonist.
12. The emulsion of claim 11 wherein the ligand is an antibody or fragment thereof.
13. The emulsion of claim 9 wherein the therapeutic agent is a drug or a radioactive agent.
14. The emulsion of claim 13 wherein the drug is tissue plasminogen activator, adriamycin, vincristine, urokinase, streptokinase, methotrexate, cytarabine, thioguanine, 5-fluorouracil, cisplatin, etoposide, ifosfamide, asparaginase, deoxycoformycin or hexamethyl melamine.
15. The method of claim 1 wherein said perfluorocarbon consists of perfluorotributylamine, perfluorodecalin, perfluorooctylbromide, perfluorodichlorooctane, perfluorodecane, perfluorotripropylamine, perfluorotrimethylcyclohexane, or mixtures of the foregoing.